Abstract

Type I IFN subtypes have been shown to exhibit differential efficacies in the immune response to virus infections. Recent efforts in vaccine developments have focused on new strategies to improve immunity, including the interaction of dendritic cells (DC) with IFNs. In this study, we assess the immunomodulating capacity of a panel of mouse IFN proteins to enhance DC activation and immune stimulating potential, providing a link between innate and adaptive immunity. Individual or combinatorial murine IFN-alpha and -beta subtypes were used to stimulate BALB/c bone marrow-derived DC (BMDC), which were then analysed for activation marker expression, antigen uptake and processing, and antigen-specific CD4_ T cell stimulatory capacity. Murine IFN-alpha 1, -4, -6 and beta subtypes displayed differential efficacies in BMDC activation, antigen processing and presentation to naïve antigen-specific CD4_ T cells. IFN-beta was the most efficient stimulator of BMDC activation and antigen processing of all the subtypes tested, followed by IFN-alpha 4. Additionally, IFN-alpha 4/beta was found to be superior to all other IFNs in enhancing antigen processing. However, IFN treatment appeared to inhibit DC-mediated CD4_ T cell activation in an ovalbumin model system. Differences in mRNA expression profiles of TLR-3, -4, -9, OAS1, PKR and RIG-I after BMDC stimulation with IFN subtypes were noted. These data confirm the adjuvant potential of select IFN subtypes in DC-mediated immunity and propose their application for vaccine development.